Alifah Hasna, Belinda Anasthasya Tansy, Armansyah Maulana Harahap, Maulana Bagus Adi Cahyono, Edwin Hadinata, Raymond Rubianto Tjandrawinata, Fahrul Nurkolis, Lucia De Luca, Giulia Basile, Raffaele Romano, Antonello Santini
This review aims to comprehensively examine spent coffee grounds (SCGs) as a sustainable source of antioxidant and immunomodulatory bioactives, with a specific focus on their capacity to modulate membrane-level signaling through ion channels and G-protein-coupled receptors (GPCRs) in the context of lifestyle-related chronic diseases. SCGs, the major solid by-product of coffee brewing, represent an underutilized yet highly abundant source of bioactive compounds, including chlorogenic acids, phenolic acids, melanoidins, diterpenes, and residual alkaloids. Lifestyle-related chronic diseases, including type 2 diabetes, obesity, cardiovascular disease, and chronic inflammatory disorders, are increasingly recognized as immunometabolic conditions driven by persistent low-grade inflammation, redox imbalance, and dysregulated membrane signaling. This review synthesizes current evidence demonstrating that bioactives contained in SCG extracts exert antioxidant and immunomodulatory effects that extend beyond radical scavenging. Crucially, these compounds also act as modulators of membrane-level signaling, representing a mechanistic perspective that has not been previously integrated for SCGs in the context of chronic disease. The different extraction methodologies and the obtained results are evaluated with the aim to identify the most effective experimental approach and extraction conditions. The paper also discusses how SCG compounds regulate redox-sensitive ion channels (including calcium channels, TRP channels, and potassium channels), and key GPCR pathways (such as GPR120, GPR43, and adenosine receptors), thereby influencing immune cell activation, cytokine production, insulin signaling, and metabolic inflammation. Particular attention is given to the role of microbial fermentation and enzymatic processing in enhancing SCG bioavailability, generating postbiotic metabolites that further engage GPCR–ion channel crosstalk. By integrating extraction approaches, antioxidant chemistry, immunology, membrane signaling, and nutritional metabolism, this review positions SCG as a sustainable functional ingredient capable of restoring immune tolerance and metabolic homeostasis. These insights support the valorization of SCGs within the circular economy framework and highlight their potential application in next-generation immunonutrition strategies for chronic disease prevention and management. © 2026 by the authors.
Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, 60131, Indonesia; School of Medicine, Faculty of Medicine, Universitas 17 Agustus 1945 (UNTAG) Surabaya, Surabaya, 60118, Indonesia; Department of Physical Education, Health and Recreation, Faculty of Sport, Universitas Negeri Medan, Medan, 20221, Indonesia; Medical Program, Faculty of Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia; School of Medicine, Faculty of Medicine, Ciputra University of Surabaya, Surabaya, 60219, Indonesia; School of Bioscience, Innovation and Technology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia; Medical Research Center of Indonesia, Surabaya, 60281, Indonesia; Institute for Research and Community Service, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, Indonesia; Department of Agricultural Sciences, University of Napoli Federico II, Piazza Carlo di Borbone 1, Portici, 80055, Italy; Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano, 49, Napoli, 80131, Italy
